Results of a recently published study show that a steroid-free regimen of Velcade and thalidomide is effective in newly diagnosed multiple myeloma patients.

This finding is particularly significant for patients who are unable to tolerate treatment with steroids due to their side effects, according to the study’s lead author Dr. Ivan Borello from the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center in Baltimore,

“The purpose of this study was to develop a therapy that could be used for patients in whom steroids for one reason or another were contraindicated.  Those would include patients with significant diabetes, in whom the psychological effect of steroids is significant, history of gastrointestinal bleeding, etc,” said Dr. Borrello. 

“I believe that what we showed is that this regimen is a viable option for many of these patients, and those are the individuals in whom we are offering such a regimen,” he added.

However, Dr. Borello and his colleagues pointed out that a randomized Phase 3 clinical trial directly comparing two regimens, one with steroids and one without, is needed to confirm the study results.

Since the introduction of novel therapeutic agents, such as Velcade (bortezomib) thalidomide (Thalomid), and Revlimid (lenalidomide), response rates and survival have increased for multiple myeloma patients.

The novel agents are often used in combination with corticosteroids, such as dexamethasone (Decadron) and prednisone. Research has shown that, in newly diagnosed patients, the novel agent Velcade is more than twice as effective in combination with dexamethasone than as a single agent (88 percent versus 40 percent).

However, this improvement in efficacy is somewhat limited by the side effects that accompany treatment with steroids. Steroids are associated with an increased risk of blood clot formation. Patients are therefore typically prescribed medication to prevent the formation of clots. In some cases, myeloma patients (primarily elderly patients) are unable to be treated with steroids due to serious side effects.

As a result, Dr. Borrello and his colleagues designed a Phase 2 clinical trial to evaluate the efficacy and safety of a steroid-free treatment regimen for myeloma patients.

They included 30 newly diagnosed patients in their study. The median age of the study participants was 58 years.

Patients received 1.3 mg/m² of Velcade on days 1, 4, 8, and 11 of a 21-day cycle and a starting dosage of 50 mg of thalidomide once daily, which was increased by 50 mg each week to a maximum dose of 150 mg per day. The researchers did not use the standard maximum thalidomide dosage of 200 mg because both Velcade and thalidomide cause considerable side effects to the nervous system.

Out of 27 patients who were evaluable for results, 22 (81 percent) responded to the Velcade-thalidomide treatment, with three patients achieving a complete response and four achieving a near complete response.

The median time to response was 1.2 months. The median progression-free survival was 16.8 months, with 20 patients living more than three years after treatment started. Median overall survival had not been reached yet at the time of data analysis.

In order to determine the effect of steroids on patient response rates, Dr. Borello and his colleagues compared the Velcade-thalidomide (VT) response rate with a Velcade-thalidomide-dexamethasone (VTD) response rate reported in a separate study. The VTD response rate was slightly higher, which, according to the study authors, may be explained by dexamethasone’s anti-myeloma activity.

However, it is still unclear how dexamethasone impacts patient survival, and the researchers noted that the significant anti-myeloma activity of the VT regimen itself is still promising for patients who experience serious side effects with even low-dose steroids (mostly elderly patients).

The most commonly reported serious side effect was peripheral neuropathy, which is characterized by pain and tingling in the extremities. Six patients (22 percent) developed serious peripheral neuropathy, and 13 patients (48 percent) reported moderate peripheral neuropathy.

However, the study authors pointed out that peripheral neuropathy was reversible in 80 percent of the patients once they discontinued treatment.

The researchers hypothesized that neuropathy could potentially be reduced with lower dosages of Velcade and thalidomide, less frequent administration of the drugs, or a combination treatment consisting of Velcade and Revlimid.

The researchers did not observe any incidents of blood clot formation, a frequent side effect of steroid-containing therapies.

For more information, please see the full study in the British Journal of Haematology (abstract).